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Background Rilonacept, a once‐weekly interleukin‐1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin‐1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long‐term extension further explored recurrent pericarditis natural history and treatment duration decision‐making during 24 additional months of open‐label rilonacept treatment. Methods and Results Seventy‐four patients commenced the long‐term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off‐treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18‐month decision milestone was 0.04 events/patient‐year versus 4.4 events/patient‐year prestudy while on oral therapies. At the 18‐month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18‐month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P

Abstract Objective Amyloidosis due to the transthyretin Ser77Tyr mutation (ATTRS77Y) is a rare autosomal‐dominant disorder, characterized by carpal‐tunnel syndrome, poly‐ and autonomic‐neuropathy, and cardiomyopathy. However, related symptoms and signs are often nonspecific and confirmatory tests are required. We describe the age and frequency of early symptoms and diagnostic features among individuals of Jewish Yemenite descent in Israel. Methods Records of mutation carriers were retrospectively reviewed. ATTRS77Y diagnosis was defined by the presence of amyloid in tissue and/or amyloid‐related cardiomyopathy. Results We identified the Ser77Tyr mutation at the heterozygous state in 19 amyloidosis patients (mean age at diagnosis: 62 ± 5.7 years, range 49–70) and 30 amyloid‐negative carriers. The probability for disease diagnosis increased from 4.4% at age 49 to 100% at 70 and occurred earlier in males. Initial symptoms preceded diagnosis by 5 ± 3.8 years (range 0–12) and were commonly sensory changes in the extremities. Erectile dysfunction predated these in 8/13 (62%) males. In two patients cardiac preceded neurological symptoms. Two patients declined symptoms. Electrophysiological studies near the time of diagnosis indicated a median neuropathy at the wrist in 18/19 (95%) and polyneuropathy in 13/19 (68%). Skin biopsy revealed epidermal denervation in 15/16 (94%) patients. Cardiomyopathy was identified in 16/19 (84%). Sensory complaints or epidermal denervations were present in 17/30 (57%) of amyloid‐negative carriers and co‐occurred in 10/30 (33%). Interpretation ATTRS77Y symptoms commonly occur after age 50, but may begin earlier. Median neuropathy, skin denervation and cardiomyopathy are frequently identified. Symptoms may be absent in patients and common in amyloid‐negative carriers.

Abstract Aims To describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes. Methods and results Our registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing‐risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all‐cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1–10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF. Conclusions Hypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.

Abstract Aims To assess the effect of angiotensin receptor blockers/neprilysin inhibitors (ARNI) on left ventricular (LV) ejection fraction (LVEF) and LV dimensions in a real‐life cohort of heart failure and reduced ejection fraction (HFrEF) patients, while analysing patient characteristics that may predict reverse LV remodelling. Methods and results The ARNI‐treated HFrEF patients followed at a single tertiary medical centre HF‐outpatient clinic were included in the study. Clinical and echocardiographic parameters were evaluated prior to ARNI initiation, and while on ARNI therapy, assessing patient characteristics associated with reverse LV remodelling. The cohort included 91 patients (mean age 60.5 years, 90% male) and 47 (52%) patients exhibited ARNI responsiveness, defined as an increase in LVEF during therapy. Overall, LVEF increased by 19% post‐ARNI (23.8 to 28.4%, P

Background: Vaccines against SARS-COV2 have been crucial in efforts against COVID19, yet there have been reports of pericarditis following vaccination with mRNA-based vaccines. Methods: We questioned consecutive patients with a history of acute pericarditis (AP) evaluated in the pericardial disease clinic during 3–11/2020 in a single tertiary center. Patients with significant myocardial involvement or pericarditis secondary to another systemic disease were excluded. Results: We included 64 patients in the final analysis. Mean age was 53.1 (±18), and 26 (41%) were female. At least 1 recurrence of AP was documented in 47 (73%) cases, 32 (50%) had ≥ 3 recurrences prior to vaccination. AP was considered to be idiopathic/viral in 45 (70%) cases, 20 (31%) cases were post-injury. All patients received at least 2 doses of the vaccine, and 48 patients (75%) received a 3rd dose. Two cases of breakthrough COVID19 infections were documented. Overall, 12 patients (19%) reported any adverse events. Of which, 2 had recurrent pericarditis. There was a trend for a younger age in those patients who had adverse events (median age 45 [IQR 36–61] vs. 60 [38–71], p = 0.08). no other significant difference was seen. Conclusion: In patients with a history of acute ecurrent pericarditis, the use of BNT162b2 was mostly uneventful, but some mild disease recurrences did occur.

Abstract Objectives To evaluate the effect of monetary grants on young physicians’ choice of remote or rural hospital-based practice. Background In late 2011, The Israeli Ministry of Health attempted to address a severe physician maldistribution, which involved severe shortages in remotely-located institutions (RLI). The policy intervention included offering monetary grants to residents who chose a residency program in a RLI. Methods A total of 222 residents from various disciplines were recruited; 114 residents from RLI and 108 residents from central-located institutions (CLI), who began their residency during 2012–2014. Participants were surveyed on demographic, academic and professional data, and on considerations in the choice of residency location. Results Residents in RLI attributed significantly more importance to the grant in their decision-making process than did residents from CLI. This effect remained significant in a multivariate model (OR 1.65, 95% CI 1.20–2.27, p = 0.002). The only parameter significantly associated with attributing importance to the grant was older age (OR 1.09, 95% CI 1.00–1.19, p = 0.049). Conclusion The choice of a RLI for residency may be influenced by monetary grants. This is consistent with real-life data showing an increase in medical staffing in these areas during the program’s duration. Further studies are needed to determine causality and physical practicality of such programs.

Background/Objective: Objective assessment tools for patients' frailty are lacking. Such tools would have been highly valuable for assessment of candidates for cardiac rehabilitation programs. Low ALT (Alanine aminotransferase) values were recently shown to be a promising parameter for objective, quantitative frailly assessment. Methods: This was a retrospective study of patients participating in a cardiac rehabilitation program. Results: Patients with lower ALT activity levels at the initiation of rehabilitation program had lower estimated METs values (6.86 vs. 7.73; p

Introduction: The combination of acute/sub-acute neurological and metabolic derangements should always raise the suspicion of toxicity, either endogenous or exogenous. The adverse effects of psychiatric medications are especially difficult to determine since the psychiatric background of patients is often inaccessible. Clinical Presentation: A 66-year-old man presented to the emergency department with dysarthria and uncontrolled tremor, rapidly deteriorating into a complex of severe neurological and metabolic derangements. Only after repeated attempts to take a thorough history was lithium toxicity identified. Conclusion: Thorough, comprehensive history taking, including chronic medications and their substitutes, is essential and lifesaving when potentially lethal medications are involved.